Objectives <p>This research involves the development, synthesis, in-silico ADMET and molecular docking studies, and in-vitro anti-inflammatory analysis of chalcone-linked pyrazole amine compounds.</p> Methods <p>This study focuses on the synthesis of pyrazole-fused chalcone amine derivatives via molecular hybridization. Two synthetic series were designed, each using different hydrazide and amine derivatives, resulting in a library of 100 compounds. In-silico ADMET analysis and molecular docking studies were conducted via different tools for all compounds, leading to the selection of six derivatives based on their scores. These selected compounds were synthesized and subsequently evaluated in-vitro for anti-inflammatory activity using the egg albumin protein denaturation method.</p> Results <p>The structural identification of the synthesized chalcone-linked pyrazole amine derivatives was confirmed through FT-IR, ¹H NMR, ¹³C NMR, and MASS, with the observed peaks consistent with the expected products. These compounds were selected based on favorable ADMET and molecular docking scores obtained from in-silico analyses using various computational tools. In-vitro anti-inflammatory evaluation suggests that these derivatives hold significant potential as anti-inflammatory agents, likely due to the synergistic effects of the pyrazole-fused chalcone moiety.</p> Conclusion <p>In conclusion, pyrazole-fused chalcone amine derivatives were successfully synthesized and validated, showing promising in-silico and in-vitro anti-inflammatory activity, making them potential candidates for further development as anti-inflammatory agents.</p> Graphical Abstract <p></p>